Penetration of lipid bilayers by nanoparticles with environmentally-responsive surfaces: simulations and theory

Understanding the interactions between nanoparticles (NPs) and lipid bilayers is critical for the design of drug delivery carriers, biosensors, and biocompatible materials. In particular, it is desirable to understand how to effectively translocate synthetic molecules through the cellular membrane, which acts as a selective barrier to regulate transport into the cell. In this work, we use simulations and theory to explore the role that surface reconstruction may play in non-specific interactions between NPs and lipid bilayers. We show that NPs with a mixed hydrophobic/hydrophilic surface functionalization capable of rearranging their surfaces to maximize hydrophobic matching with the bilayer core are able to spontaneously establish a thermodynamically-favored position at the bilayer midplane. Furthermore, this penetration behavior is most favorable thermodynamically when the surface of the NP is near an order-disorder transition. Our analysis provides design criteria for future synthetic NPs, with the goal of designing particles that can maintain a stable transmembrane orientation.